Abemaciclib mesylate (LY2835219)

Description

Abemaciclib (1231930-82-7) is a potent and selective CDK4/6 inhibitor (IC50?= 2 nM and 10 nM respectively).1?It caused G1 cell cycle arrest in colo-205 colorectal cells, MDA-MB-361 breast cancer cells, and MV4-11 AML cells. Abemaciclib was also active in several human tumor xenograft models. It displayed efficacy in patients with various solid tumors including breast cancer, non-small cell lung cancer. Glioblastoma, melanoma, colorectal cancer, and hormone receptor-positive breast cancer.2?Abemaciclib induced a T cell inflamed tumor microenvironment and enhanced the efficacy of PD-L1 checkpoint blockade in MCF-7 breast cancer cells.3?FDA approved for the treatment of advanced breast cancers.

The Uses of Abemaciclib mesylate (LY2835219)

LY2835219 is an orally-bioavailable dual inhibitor of cyclin-dependent kinase 4 (CDK4) and CDK6 (IC50s = 2 and 10 nM, respectively). Through this mechanism, it blocks phosphorylation of retinoblastoma protein, resulting in arrest of cell cycling in the G1 phase. LY2835219 has antitumor action against xenografts when used alone or in combination with other chemotherapeutic compounds.[Cayman Chemical]

The Uses of Abemaciclib mesylate (LY2835219)

N-[5-[(4-Ethyl-1-piperazinyl)methyl]-2-pyridinyl]-5-fluoro-4-[4-fluoro-2-methyl-1-(1-methylethyl)-1H-benzimidazol-6-yl]-2-pyrimidinamine is an CDK4/6 protein kinase inhibitor with potential antitumor effects.

Enzyme inhibitor

This oral cell cycle inhibitor (FWfree-base = 506.61 g/mol; FWmesylate-salt = 602.70 g/mol; CAS 1231930-82-7 (mesylate salt)), also known as LY2835219 and N-[5-[(4-ethyl-1-piperazinyl)methyl]-2-pyridinyl]-5- fluoro-4-[4-fluoro-2-methyl-1-(1-methylethyl)-1H-benzimidazol-6-yl]-2- pyrimidinamine, targets the cyclin-dependent kinase CDK4, or cyclin D1 (IC50 = 2 nM) and CDK6, or cyclin D3 (IC50 = 6 nM), inhibiting retinoblastoma (Rb) protein phosphorylation in early G1, thereby arresting the cell cycle in the G1, suppressing DNA synthesis, and inhibiting cancer cell growth. LY2835219 inhibits activation of AKT and ERK, but not mTOR.

References

1) Gelbert?et al.?(2014),?Preclinical characterization of the CDK4/6 inhibitor LY2835219: In-vivo cell cycle-dependent/independent anti-tumor activities alone/in combination with gemcitabine; Invest. New Drugs,?32?825 2) Patnail?et al.?(2016),?Efficacy and Safety of Abemaciclib, an Inhibitor of CDK4 and CDK6, for Patients with Breast Cancer, Non-small Cell Lung Cancer, and Other Solid Tumors; Cancer Discov.,?6?740 3) Schaer?et al. (2018),?The CDK4/6 Inhibitor Abemaciclib Induces a T Cell Inflamed Tumor Microenvironment and Enhances the Efficacy of PD-L1 Checkpoint Blockade; Cell Rep.,?22?2978